This application seeks renewal of an Independent Scientist Award to permit the candidate to devote full time effort to human research and research mentoring with the goal of improving alcoholism treatment by developing better methods of psychosocial and pharmacological treatments. To this end, the applicant has followed two paths: clinical studies of naltrexone in combination with psychotherapy and laboratory studies designed to examine the effects of these same medications on responses to alcohol and alcohol self-administration. Using these methods, future research efforts will focus on pharmacotherapies, such as acamprosate, that target other aspects of alcohol dependence and may be effective alone or in combination with naltrexone. The renewal of the K02 award will include an expanded emphasis on abstinence initiation and withdrawal symptomatology, and medications the purport to attenuate protracted withdrawal, and advanced statistical techniques to evaluate change. The Research Plan provides a detailed description of a laboratory study designed to provide critical information about the effects of acamprosate on central aspects of alcohol dependence: withdrawal and loss of control drinking. Acamprosate is approved for treatment in Europe based on studies showing that acamprosate improved rates of abstinence. However, there is little information regarding whether acamprosate reduces relapse following a lapse and on whether acamprosate attenuates withdrawal as hypothesized. One hundred-twenty nontreatment seeking alcohol dependent volunteers will be randomized to receive placebo or one of two doses of acamprosate and studied in the laboratory to assess the effects of the medication on alcohol withdrawal symptomatology, alcohol intoxication and alcohol self-administration. Better characterization of these effects will be important for determining the optimal sequencing and timing of pharmacotherapies such as acamprosate and for increasing the overall success rate for achieving and maintaining abstinence. The Career Development Plan include collaborations with investigators at the Scripps Institute, Brown University and the University of Missouri and selected course work in statistical methods. The objective of the career development plan will be to acquire an understanding of preclinical models to study homeostatic mechanisms involved in addiction and the effect of pharmacological interventions during acute withdrawal, protracted withdrawal, and relapse. In addition, a major objective will be to acquire training in statistical methods appropriate for the analysis of change and mediational processes in longitudinal data sets, including hierchical linear modeling, repeat event time analysis, regression analyses, and structural equation modeling.